Abstract
One-fourth of the human population is estimated to have been exposed to Mycobacterium tuberculosis (Mtb) and carries the infection in its latent form. This latent infection presents a lifelong risk of developing active tuberculosis (TB) disease, and persons with latent TB infection (LTBI) are significant contributors to the pool of active TB cases. Genetic polymorphisms among hosts have been shown to contribute to the outcome of Mtb infection. The SP110 gene, which encodes an interferon-induced nuclear protein, has been shown to control host innate immunity to Mtb infection. In this study, we provide experimental data demonstrating the ability of the gene to control genetic susceptibility to latent and active TB infection. Genetic variants of the SP110 gene were investigated in the Taiwanese population (including 301 pulmonary TB patients, 68 LTBI individuals, and 278 healthy household contacts of the TB patients), and their association with susceptibility to latent and active TB infection was examined by performing an association analysis in a case-control study. We identified several SNPs (rs7580900, rs7580912, rs9061, rs11556887, and rs2241525) in the SP110 gene that are associated with susceptibility to LTBI and/or TB disease. Our studies further showed that the same SNPs may have opposite effects on the control of susceptibility to LTBI versus TB. In addition, our analyses demonstrated that the SP110 rs9061 SNP was associated with tumor necrosis factor-α (TNFα) levels in plasma in LTBI subjects. The results suggest that the polymorphisms within SP110 have a role in controlling genetic susceptibility to latent and active TB infection in humans. To the best of our knowledge, this is the first report showing that the SP110 variants are associated with susceptibility to LTBI. Our study also demonstrated that the identified SP110 SNPs displayed the potential to predict the risk of LTBI and subsequent TB progression in Taiwan.
Highlights
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the top ten causes of death in the world [1]
To investigate the association between the SP110 gene and control of Mtb infection, we examined polymorphisms in the gene of members of the Taiwanese population for genetic association with TB disease status
We found that 3 singlenucleotide polymorphisms (SNPs) showed differential allele frequency distributions in latent TB infection (LTBI) cases vs. healthy controls (Table 2)
Summary
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the top ten causes of death in the world [1]. One-fourth of the world population has been infected with Mtb [2], but only 10% of these infected persons develop progressive disease during their lifetimes [3]. The majority of infected individuals remain healthy and noninfectious but carry Mtb in a latent form. As many as 10% of people with LTBI will go on to develop progressive disease in the near or remote future (a process named “TB reactivation”), and the risk is significantly higher in the presence of predisposing factors, such as coinfection with human immunodeficiency virus (HIV).
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